ArticleThe Journal of clinical investigation2015
UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 153 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
153 citing papers in PubMed, 238 citations in OpenAlex.
- Hyperinflammation by Human Macrophages Induced by SARS-CoV-2 Anti-Spike IgG Is Dependent on Glucose and Fatty Acid Metabolism.European journal of immunology · 2025Article
- Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3/ IL-1β pathway.Journal of advanced research · 2025Article
- The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases.Archives of toxicology · 2025Review
- Lipid Metabolism: An Emerging Player in Sjögren's Syndrome.Clinical reviews in allergy & immunology · 2025Review
- Circadian metabolic adaptations to infections.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Metformin Ameliorates Ulcerative Colitis Through Inhibiting NLRP3 Inflammasome Activation.Journal of inflammation research · 2025Article
- HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV.Brain, behavior, and immunity · 2025Article
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- A New Strategy for Targeting UCP2 to Modulate Glycolytic Reprogramming as a Treatment for Sepsis A New Strategy for Targeting UCP2.Inflammation · 2024Review
- The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis.Science immunology · 2024Article
- Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway.Cell communication and signaling : CCS · 2024Article
- Article
- Emerging nanomaterials targeting macrophage adapted to abnormal metabolism in cancer and atherosclerosis therapy (Review).International journal of molecular medicine · 2024Review
- The implications of FASN in immune cell biology and related diseases.Cell death & disease · 2024Review
- Immunometabolic Rewiring: A Tale of Macronutrients and Macrophages.Results and problems in cell differentiation · 2024Review
- Review
- Theaflavin mitigates acute gouty peritonitis and septic organ injury in mice by suppressing NLRP3 inflammasome assembly.Acta pharmacologica Sinica · 2023Article
- Pitfalls of Mitochondrial Redox Signaling Research.Antioxidants (Basel, Switzerland) · 2023Review
- The NLRP3 inflammasome: role in the pathobiology of chronic pain.Inflammopharmacology · 2023Review
- ATP-citrate lyase controls endothelial gluco-lipogenic metabolism and vascular inflammation in sepsis-associated organ injury.Cell death & disease · 2023Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2023-03-15Investigation by Company/Institution · Unreliable Data · Unreliable Image ·
- Retracted
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1-dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro-IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.